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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the differences between the action of haloperidol and pimozide on dopamine metabolism and on catalepsy in periods up to 6 weeks after cessation of chronic administration of the neuroleptics to male Wistar rats. Dopamine and its metabolites (dihydroxyphenylacetic and homovanillic acids) were measured, using high-performance liquid chromatography (HPLC), in the frontal cortex, nucleus accumbens, and striatum. Both neuroleptics produced similar effects after a single dose: catalepsy and an increase of dopamine metabolism in the brain structures. However, haloperidol and pimozide differed after chronic treatment. In haloperidol-treated rats hypersensitivity of the dopaminergic system developed at the end of 2 weeks' administration, as evidenced by depression of dopamine metabolism. The biochemical changes were accompanied by behavioral hyperactivity that lasted up to 3 weeks. Dopamine metabolism in rats treated with pimozide was normal from 24 h after the end of the treatment, while catalepsy was maintained at the high level for up to 8 days and was observable up to 3 weeks after the last dose. Our results suggest that in contrast to haloperidol, pimozide is not able to produce adaptive changes leading to supersensitivity of the dopaminergic system. This may be the consequence of its potent Ca2+ channel blocking action.
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PMID:Different effects of chronic administration of haloperidol and pimozide on dopamine metabolism in the rat brain. 891 13

Dopamine D1 and D2 receptors were measured (by saturation binding of [3H]SCH23390 and [3H]raclopride) in caudate, putamen and nucleus accumbens, obtained at post-mortem from suicide victims with a firm retrospective diagnosis of depression, and matched controls. There were no differences in the number or affinity of D1 or D2 receptors between suicides who had been free of antidepressants for at least three months prior to death, and controls. Increased numbers and decreased affinity of D2 receptors were however found in each brain region of antidepressant-treated suicides. We argue that these increases are related to concurrent treatment with neuroleptics rather than a direct effect of antidepressants. Increased numbers of D1 receptors in antidepressant-treated suicides were seen only in nucleus accumbens. This increase could not be clearly attributed to neuroleptics and may be related to antidepressant treatment.
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PMID:Dopamine D1 and D2 receptor binding sites in brain samples from depressed suicides and controls. 910 61

Dopamine D2 receptors (D2Rs) are of crucial importance in the striatal processing of motor information received from the cortex. Disruption of the D2R gene function in mice results in a severe locomotor impairment. This phenotype has analogies with Parkinson's disease symptoms. D2R-null mice were used to investigate the role of this receptor in the generation of striatal synaptic plasticity. Tetanic stimulation of corticostriatal fibers produced long-term depression (LTD) of EPSPs in slices from wild-type (WT) mice. Strikingly, recordings from D2R-null mice showed the converse: long-term potentiation (LTP). This LTP, unlike LTD, was blocked by an NMDA receptor antagonist. In magnesium-free medium, LTP was also revealed in WT mice and found to be enhanced by L-sulpiride, a D2R antagonist, whereas it was reversed into LTD by LY 17555, a D2R agonist. In D2R-null mice this modulation was lost. Thus, our study indicates that D2Rs play a key role in mechanisms underlying the direction of long-term changes in synaptic efficacy in the striatum. It also shows that an imbalance between D2R and NMDA receptor activity induces altered synaptic plasticity at corticostriatal synapses. This abnormal synaptic plasticity might cause the movement disorders observed in Parkinson's disease.
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PMID:Abnormal synaptic plasticity in the striatum of mice lacking dopamine D2 receptors. 916 14

Lateral hypothalamic area dopamine activity (LHA-DA) appears to play a contributory role in regulating food intake, in particular, meal size. In this study we examined our hypothesis that bilateral LHA-DA injection induced depression of food intake via reduced meal size. Dopamine (11 mg/ml) or vehicle was infused into bilateral LHA at 0.5 microliter/h via two osmotic minipumps in six study or six control obese male Zucker rats for 13 days, respectively. Meal size, meal number, as well as food intake were continuously measured before, during, and after dopamine infusion. Intra-LHA-DA infusion significantly depressed food intake. The decreased food intake was solely caused by a significant and profound reduction in meal size. There was a modest compensatory rise in meal number that gradually increased food intake so that it reached control level on 10th dopamine infusion day. However, feeding pattern did not normalize until dopamine infusion ceased. The findings support our hypothesis that LHA-DA may participate in regulating meal size. Data also demonstrate that meal size and meal number are regulated in a reciprocal and independent manner to compensate for each other.
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PMID:Bilateral hypothalamic dopamine infusion in male Zucker rat suppresses feeding due to reduced meal size. 932 51

The dopaminergic system is a candidate neurotransmitter system thought to be involved in the pathogenesis of depression. This study addresses the issue whether the antidepressant efficacy of serotonin reuptake inhibition is related to changes in the cerebral dopaminergic system. Cerebral dopamine-D2 receptors were characterized in 13 patients with major depression using the dopamine-D2 receptor antagonist iodobenzamide and single photon emission tomography. Dopamine receptor binding was assessed twice, before and during serotonin reuptake inhibition. An increase in dopamine-D2 receptor binding during serotonin reuptake inhibition was found in striatum and anterior cingulate gyrus in treatment responders, but not in nonresponders. The increase in dopamine-D2 receptor binding correlated significantly with clinical recovery from depression as assessed with the Hamilton depression scale (r = 0.59 for right and left striatum respectively, P < 0.05; r = 0.79 for the anterior cingulate gyrus, P < 0.05 after Bonferroni correction). Qualitatively similar correlations were observed in the precentral gyrus, the medial frontal gyrus, the inferior frontal gyrus, and the frontal part of the opercular gyrus, but these correlations failed to reach statistical significance after correction for the effects of multiple testing. No such correlations were found in the superior frontal gyrus, the orbitofrontal gyrus, the gyrus rectus, the superior parietal gyrus, or the superior temporal gyrus. The data strengthen the concept that the striatum and the anterior cingulate gyrus are involved in mood regulation. Dopamine-D2 receptors may constitute a central role in this domain.
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PMID:In vivo evidence for the involvement of dopamine-D2 receptors in striatum and anterior cingulate gyrus in major depression. 934 54

The evaluation, treatment and care of patients with dementia are major tasks for the health service. This paper provides an overview of drug treatment of the emotional and cognitive disturbances of dementia. Tricyclic and the newer anti-depressive agents are effective in patients with dementia and depression. Dopamine-blocking agents are effective for some patients with dementia and psychosis, but their use is limited by frequent and severe side-effects. Atypical neuroleptics may prove useful for this patient group. Aggression and agitation may be treated with serotonergic agents, neuroleptics, or benzodiazepines, but other strategies may also be useful. Cholinesterase-inhibitors have demonstrated efficacy on cognition and function, and may reduce the likelihood of institutionalization. Studies of possible stabilization therapies, such as trophic factors, propentophylline, and antiamyloid drugs, are reviewed. Recent reports suggesting a possible prophylactic effect of antioxidants, oestrogen, and antiinflammatory drugs are discussed. The substantial efforts now being made to discover effective drugs for dementia suggest that compounds that delay the disease progression may be available in the next 5-10 years.
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PMID:[Drug treatment of emotional and cognitive dysfunction in dementia]. 952 May 84

Dopaminergic agents and stimulants have been used to manage depression when conventional antidepressant treatments fail. We reviewed evidence for the role of dopaminergic dysfunction in depression, the use of dopaminergic agents as antidepressants, and the use of dopaminergic agents and stimulants as antidepressant adjuncts. Dopamine may be part of the pathophysiology of depression for a subset of patients. When used with caution and an appreciation of the potential risk of abuse, dopaminergic agents and stimulants may be useful for patients refractory to antidepressants alone.
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PMID:Dopaminergic agents and stimulants as antidepressant augmentation strategies. 963 49

Using sharp-electrode intracellular recordings, we studied the dopaminergic facilitation of synaptic plasticity in layer I-II afferents--layer V neuron glutamatergic synapses in rat prefrontal cortex in vitro. Tetanic stimulation (100 pulses at 50 Hz, four times at 0.1 Hz) to layer I-II afferents induced N-methyl-D-aspartate receptor-independent long-term depression (>40 min) of the glutamatergic synapses when the stimulation was coupled with a bath-application of dopamine. Tetanic stimulation alone did not induce lasting synaptic changes. Dopamine application alone transiently depressed synaptic responses, which fully recovered within 30 min. Pharmacological analyses with antagonists suggested that dopamine action on either D1-like or D2-like receptors can facilitate the induction of long-term depression. However, results with agonists were not fully consistent with the antagonist results: while a D2 agonist mimicked the facilitatory dopamine effect, D1 agonists failed to mimic the effect. We also analysed the synaptic responses during tetanus and found that dopamine prolongs membrane depolarization during high-frequency inputs. Postsynaptic membrane depolarization is indeed critical for long-term depression induction in the presence of dopamine, since postsynaptic hyperpolarization during tetanus blocked the dopaminergic facilitation of long-term depression induction. Postsynaptic injection of the Ca2+ chelator bis-(o-aminophenoxy)-N,N,N',N'-tetra-acetic acid (100 mM in the electrode) also blocked long-term depression induction. Our results show that dopamine lowers the threshold for long-term depression induction in rat prefrontal glutamatergic transmission. A possible underlying mechanism of this dopaminergic facilitation is the enhancement of postsynaptic depolarization during tetanus by dopamine, which may increase the amount of Ca2+ entry from voltage-gated channels to the level sufficient for plasticity induction.
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PMID:Dopamine facilitates long-term depression of glutamatergic transmission in rat prefrontal cortex. 963 64

Two girls with florid extrapyramidal parkinsonism complicating systemic lupus erythematosus (SLE) are reported. One patient (15 years old) presented with extreme rigidity, irritability, and mutism initially diagnosed as acute psychosis. Examination revealed severe extrapyramidal akinetic mutism, along with marked restlessness. CT and MRI imaging of the brain were unremarkable. EEG revealed moderate generalized disturbance of background activity. 99mTc-HmPAO SPECT cerebral scanning detected decreased regional cerebral blood flow at the basal ganglia. Dopamine-agonist drugs led to complete recovery after 3 months, along with normalization of EEG and SPECT alterations. The second patient (16 years old) was assessed for progressive bradykinesia and apathy impeding her active daily activities, and she was suspected to have developed depression. Neurologic assessment revealed a parkinsonian syndrome that was less severe than that of the first patient. The EEG showed mild disturbance of background activity, and 99mTc-HmPAO SPECT demonstrated impaired regional cerebral blood flow over the basal ganglia. A parkinsonian extrapyramidal syndrome complicating SLE should therefore be taken into account in any patient with SLE presenting with marked behavioral alterations, rigidity, or akinetic mutism.
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PMID:Parkinsonian syndrome complicating systemic lupus erythematosus. 965 Jun 92

The effects of lesions, receptor blocking, electrical self-stimulation, and drugs of abuse suggest that midbrain dopamine systems are involved in processing reward information and learning approach behavior. Most dopamine neurons show phasic activations after primary liquid and food rewards and conditioned, reward-predicting visual and auditory stimuli. They show biphasic, activation-depression responses after stimuli that resemble reward-predicting stimuli or are novel or particularly salient. However, only few phasic activations follow aversive stimuli. Thus dopamine neurons label environmental stimuli with appetitive value, predict and detect rewards and signal alerting and motivating events. By failing to discriminate between different rewards, dopamine neurons appear to emit an alerting message about the surprising presence or absence of rewards. All responses to rewards and reward-predicting stimuli depend on event predictability. Dopamine neurons are activated by rewarding events that are better than predicted, remain uninfluenced by events that are as good as predicted, and are depressed by events that are worse than predicted. By signaling rewards according to a prediction error, dopamine responses have the formal characteristics of a teaching signal postulated by reinforcement learning theories. Dopamine responses transfer during learning from primary rewards to reward-predicting stimuli. This may contribute to neuronal mechanisms underlying the retrograde action of rewards, one of the main puzzles in reinforcement learning. The impulse response releases a short pulse of dopamine onto many dendrites, thus broadcasting a rather global reinforcement signal to postsynaptic neurons. This signal may improve approach behavior by providing advance reward information before the behavior occurs, and may contribute to learning by modifying synaptic transmission. The dopamine reward signal is supplemented by activity in neurons in striatum, frontal cortex, and amygdala, which process specific reward information but do not emit a global reward prediction error signal. A cooperation between the different reward signals may assure the use of specific rewards for selectively reinforcing behaviors. Among the other projection systems, noradrenaline neurons predominantly serve attentional mechanisms and nucleus basalis neurons code rewards heterogeneously. Cerebellar climbing fibers signal errors in motor performance or errors in the prediction of aversive events to cerebellar Purkinje cells. Most deficits following dopamine-depleting lesions are not easily explained by a defective reward signal but may reflect the absence of a general enabling function of tonic levels of extracellular dopamine. Thus dopamine systems may have two functions, the phasic transmission of reward information and the tonic enabling of postsynaptic neurons.
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PMID:Predictive reward signal of dopamine neurons. 965 25


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